Connectivity Problems May Indicate Which Individuals are at Greatest Risk for Schizophrenia

Connectivity Problems May Indicate Which Individuals are at Greatest Risk for Schizophrenia

Posted: December 1, 2015

Alan Anticevic, Ph.D.

Yale University School of Medicine

2012, 2015 NARSAD Grantee

Communication problems in the brain that are associated with schizophrenia are present prior to diagnosis, according to a new study in which researchers examined neural connectivity in people with a high risk of developing the disorder. The study, published August 12 in the journal JAMA Psychiatry, found that the connectivity alterations were most severe in participants who went on to develop full psychosis within two years.

NARSAD 2015 Independent Investigator and 2012 Young Investigator Alan Anticevic, Ph.D., at Yale University, was the lead author of the study. NARSAD 2006 Distinguished Investigator and 1997 Independent Investigator Tyrone D. Cannon, Ph.D., also at Yale, was the senior author.

The team focused on connections between a relay center in the brain called the thalamus and other brain regions that are involved in both higher cognitive functions and primary sensory functions. There is good evidence that these “thalamo-cortical” networks, which are involved in a wide range of neural processing, are disrupted in people with schizophrenia. No one knew, however, if those disruptions might be detectable prior to full-blown illness and clinical diagnosis. Earlier diagnosis and evaluation of clinical risk has long been an objective of researchers and doctors, as it is thought that by treating patients early, the severity of the illness may be reduced, at least in some cases.

To test their ideas, the researchers used sophisticated emerging brain imaging methods to examine thalamo-cortical connections in 243 people who had experienced symptoms indicating they were at high risk of developing schizophrenia, as well as in 154 healthy subjects. They found that in high-risk individuals, the communication between the thalamus and the prefrontal cortex was weaker than observed in healthy study participants. Connections between the thalamus and sensory-processing regions of the brain, in contrast, were relatively stronger in high-risk individuals than they were in healthy controls. These patterns are similar to those that have been observed in people with more chronic schizophrenia.

After brain imaging, the study participants were followed for two years, during which time 21 individuals developed full psychosis and received a diagnosis of schizophrenia. (Dr. Anticevic cautions that the two diagnoses are distinct and that having psychosis does not necessarily imply that someone has schizophrenia.) Although the imaging studies had found abnormal thalamic connections in all at-risk individuals, the scientists' final analysis showed that the disruptions had been most severe in those who went on to develop full psychosis.

The study suggests that examining thalamo-cortical connectivity could help clinicians predict which individuals are most likely to progress to full psychosis, improving opportunities for early intervention.

Communication problems in the brain that are associated with schizophrenia are present prior to diagnosis, according to a new study in which researchers examined neural connectivity in people with a high risk of developing the disorder. The study, published August 12 in the journal JAMA Psychiatry, found that the connectivity alterations were most severe in participants who went on to develop full psychosis within two years.

NARSAD 2015 Independent Investigator and 2012 Young Investigator Alan Anticevic, Ph.D., at Yale University, was the lead author of the study. NARSAD 2006 Distinguished Investigator and 1997 Independent Investigator Tyrone D. Cannon, Ph.D., also at Yale, was the senior author.

The team focused on connections between a relay center in the brain called the thalamus and other brain regions that are involved in both higher cognitive functions and primary sensory functions. There is good evidence that these “thalamo-cortical” networks, which are involved in a wide range of neural processing, are disrupted in people with schizophrenia. No one knew, however, if those disruptions might be detectable prior to full-blown illness and clinical diagnosis. Earlier diagnosis and evaluation of clinical risk has long been an objective of researchers and doctors, as it is thought that by treating patients early, the severity of the illness may be reduced, at least in some cases.

To test their ideas, the researchers used sophisticated emerging brain imaging methods to examine thalamo-cortical connections in 243 people who had experienced symptoms indicating they were at high risk of developing schizophrenia, as well as in 154 healthy subjects. They found that in high-risk individuals, the communication between the thalamus and the prefrontal cortex was weaker than observed in healthy study participants. Connections between the thalamus and sensory-processing regions of the brain, in contrast, were relatively stronger in high-risk individuals than they were in healthy controls. These patterns are similar to those that have been observed in people with more chronic schizophrenia.

After brain imaging, the study participants were followed for two years, during which time 21 individuals developed full psychosis and received a diagnosis of schizophrenia. (Dr. Anticevic cautions that the two diagnoses are distinct and that having psychosis does not necessarily imply that someone has schizophrenia.) Although the imaging studies had found abnormal thalamic connections in all at-risk individuals, the scientists' final analysis showed that the disruptions had been most severe in those who went on to develop full psychosis.

The study suggests that examining thalamo-cortical connectivity could help clinicians predict which individuals are most likely to progress to full psychosis, improving opportunities for early intervention.